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Claims for Patent: 9,074,254

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Claims for Patent: 9,074,254

Title:Method of predicting a predisposition to QT prolongation
Abstract: The present invention describes an association between genetic polymorphisms in the ceramide kinase-like (CERKL) gene and a predisposition to prolongation of the QT interval, and provides related methods for the prediction of such a predisposition, the administration of QT interval-prolonging compounds to individuals having such a predisposition, and determining whether a compound is capable of inducing QT prolongation.
Inventor(s): Lavedan; Christian (Potomac, MD), Volpi; Simona (Derwood, MD), Licamele; Louis (Gaithersburg, MD), Mack; Kendra Tomino (Westminster, MD), Heaton; Callie Michelle (Washington, DC)
Assignee: Vanda Pharmaceuticals, Inc. (Washington, DC)
Application Number:12/593,419
Patent Claims: 1. A method of administering a compound to a human individual, the method comprising: determining, or having determined, from a biological specimen obtained from the individual, the individual's genotype at the single nucleotide polymorphism (SNP) locus rs993648; in the case that the individual's genotype at the rs993648 locus is AG and not associated with an increased risk of QT prolongation, administering to the individual a first quantity of iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof; and in the case that the individual's genotype at the rs993648 locus is non-AG and associated with an increased risk of QT prolongation, administering to the individual a second quantity of iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof that is less than the first quantity that would be administered to an individual having an AG genotype at the rs993648 locus.

2. The method of claim 1, further comprising: determining the individual's CYP2D6 genotype.

3. A method of administering a compound capable of prolonging a QT interval to a human individual suffering from long QT syndrome (LQTS), the method comprising: determining the individual's genotype at the single nucleotide polymorphism (SNP) locus rs993648; and administering to the individual a quantity of iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof based on the individual's genotype at the rs993648 locus, wherein an individual determined to have an AG genotype at the rs993648 locus is administered 24 mg/day of iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof and an individual determined to have a non-AG genotype at the rs993648 locus is administered less than 24 mg/day of iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof.

4. The method of claim 3, further comprising: determining the individual's CYP2D6 genotype.

5. The method of claim 1, wherein the first quantity is 24 mg/day.

6. The method of claim 1, wherein the individual is suffering from long QT syndrome (LQTS).
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